PHARMACOKINETICS AND TISSUE DISTRIBUTION OF ANTIMONY (V) AFTER MULTIPLE INTRAMUSCULAR ADMINISTRATIONS IN THE HAMSTER

The fate of pentavalent antimony (Sb) in different tissues in the body after intramuscular administration is of great interest for the future study of Sb therapy in different sitting. Pharmacokinetics and tissue distribution of antimony (Sb) were studied in the hamster after daily dose of sodium stibogluconate equivalent to 120 mg kgof Sb, administered intramuscularly for two weeks. Liver, spleen, heart, kidney and skin tissues were isolated after blood collection at the specified time. Antimony was measured in these tissues after suitable treatment, ashing and processing, by flameless atomic absorption spectrophotometry. The concentrations of Sb time profile in blood showed a linear rapid decline with elimination half life (t1/2) of 1.7 h. The concentration of drug (μg/gm) declined in a biphasic manner from almost all tissues. However, the concentrations of Sb were declined in slower fashion from the hamster tissues than from the blood. The maximum concentration of Sb was determined in the kidney tissues (3416 ± 631 μg/gm) while the lowest concentration was in the spleen (209 ± 187 μg/gm). The maximum concentration of Sb in the kidney (μg/gm) was more than 25 fold higher than that measured from  אאאא אאאא  אאאאא K  אאא  אאאא 120   L    אא K אאאאא א אא،אאא  אאאא، K  אאאאאא      א 1.7   K אא F  L  E  אא   K אאאאא א אא F 3416 + 631  L  E א F 209 + 187  L  KE אאא F  L  E  25  א F  L  KE  אא  אאאאא W א <  א < א < א < א <  א K אאאאאא  א F 6.2 – 5.2  E אאא א 3   K אאא אאא،אאאא אאאאאאאא אא K  

[1]  Malcolm Rowland,et al.  Physiologic modeling of cyclosporin kinetics in rat and man , 1991, Journal of Pharmacokinetics and Biopharmaceutics.

[2]  Chris Clausen,et al.  Lithium pharmacokinetics: Single-dose experiments and analysis using a physiological model , 1980, Journal of Pharmacokinetics and Biopharmaceutics.

[3]  S. Croft,et al.  Pharmacokinetics of Antimony in Patients Treated with Sodium Stibogluconate for Cutaneous Leishmaniasis , 2004, Pharmaceutical Research.

[4]  A. Mullen,et al.  Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals , 2003, Antimicrobial Agents and Chemotherapy.

[5]  J. Ledoux Features of the comparative pharmacokinetics of lithium; a potential application of its use in livestock farming. , 2003, Medical hypotheses.

[6]  C. Jaffe,et al.  Emergence of visceral leishmaniasis in central Israel. , 1998, The American journal of tropical medicine and hygiene.

[7]  C. Riera,et al.  Pharmacokinetics of meglumine antimoniate after administration of a multiple dose in dogs experimentally infected with Leishmania infantum. , 1998, Veterinary parasitology.

[8]  C. D. D. de Paula,et al.  [The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis]. , 1997, Revista da Sociedade Brasileira de Medicina Tropical.

[9]  J. Berman Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  J. Valladares,et al.  Disposition of antimony after the administration of N-methylglucamine antimoniate to dogs , 1996, Veterinary Record.

[11]  S. Croft,et al.  Skin uptake, distribution, and elimination of antimony following administration of sodium stibogluconate to patients with cutaneous leishmaniasis , 1995, Antimicrobial agents and chemotherapy.

[12]  D. Podzamczer,et al.  Visceral leishmaniasis in patients infected with human immunodeficiency virus. Co-operative Group for the Study of Leishmaniasis in AIDS. , 1990, The Journal of infection.

[13]  R. Pearson,et al.  Leishmania species: visceral (kala-azar), cutaneous, and mucosal leishmaniasis. , 1990 .

[14]  J. Berman,et al.  Pharmacokinetics of pentavalent antimony (Pentostam) in hamsters. , 1988, The American journal of tropical medicine and hygiene.

[15]  J. Berman Chemotherapy for leishmaniasis: biochemical mechanisms, clinical efficacy, and future strategies. , 1988, Reviews of infectious diseases.

[16]  D. Smith,et al.  Pharmacokinetics of antimony during treatment of visceral leishmaniasis with sodium stibogluconate or meglumine antimoniate. , 1988, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[17]  L. Gradoni,et al.  Canine Leishmaniasis in the Mediterranean Area and Its Implications for Human Leishmaniasis , 1986 .

[18]  P. Mormède,et al.  Pharmacokinetics and tissue distribution of lithium in chicken (Gallus domesticus). , 1981, Comparative biochemistry and physiology. C: Comparative pharmacology.

[19]  W. Hockmeyer,et al.  RENAL CLEARANCE OF PENTAVALENT ANTIMONY (SODIUM STIBOGLUCONATE) , 1980, The Lancet.

[20]  John E. Bennett,et al.  Principles and practice of infectious diseases. Vols 1 and 2. , 1979 .